TR&D1:RotatingFrameMRITechniques: ExchangeMediatedImagingBiomarkers P.I: Ravinder Reddy, PhD Co-investigators: Ravi Prakash Nanga PhD, Catherine DeBrosse BS, Arijitt Borthakur PhD, and Hari Hariharan PhD ABSTRACT The major barriers for progress in the field of biomedicine are limitations of existing methods in detecting and quantifying molecular changes during preclinical stages of disease. In this TR&D, as emphasized by several compelling collaborative projects, we propose to develop and optimize several molecular MRI biomarkers based primarily on chemical exchange phenomenon. The primary advantage of chemical exchange saturation transfer (CEST) methods is that, depending upon the rates of exchangeable spins, they inherently have an order of magnitude or greater sensitivity advantage over conventional magnetic resonance spectroscopy (MRS). In the previous funding period, we have developed several amine and hydroxyl group based CEST imaging techniques to measure endogenous metabolites from brain, skeletal muscle, heart and cartilage. While we have made significant progress, as demonstrated by the number of publications, the methods developed so far have been limited to single slice imaging with long acquisition times and suboptimal corrections of field inhomogeneities that preclude their broader application. To address these issues, in this competing proposal, we will develop and optimize 3D CEST imaging methods for amine and hydroxyl CEST imaging, with built-in provisions for radiofrequency and static field inhomogeneity measurements. Custom designed saturation pulses integrated with different 3D readout strategies will be investigated to determine the optimal method for a given application. In order to improve the temporal resolution we will also develop and optimize methods for integrated single shot z-spectrum from localized regions of tissues and evaluate its feasibility in measuring amine and hydroxyl CEST effect from different organs. Finally, we will design and evaluate a method based on the transverse relaxation (T1? and T2) enhancement by intermediate to fast exchanging systems (TRACE) and compare its performance with the conventional CEST in terms of sensitivity and temporal resolution. Successful accomplishment of these aims will lead to imaging-based biomarkers that are noninvasive and nonradioactive, with high spatial and temporal resolution. These biomarkers will aid in study of pathologies associated with neurodegeneration, neuropsychiatric disorders, oncology, cardiovascular, and musculoskeletal disease, thereby contributing to fundamental understanding and improved health care.